The thymus gland has been implicated in the pathogenesis of myasthenia gravis (MG) but its precise role remains to be elucidated. Several aberrant intrathymic immunological phenomena have been described. The thymus is traditionally not considered to be a site of antibody production but in MG it is frequently the scene of intense B cell activity. Acetylcholine receptor (AChR) antibody, and important pathogenetic factor, is a product of this thymic B cell activity. In addition, AChR, the autoantigen, is expressed on thymic cells. Thus, there is the potential for autosensitization to occur and be perpetuated in this lymphoid compartment. With the aid of an in vitro model of B cell differentiation, we will examine the functional properties of B lymphocytes and populations of immunoregulatory cells obtained from thymuses of patients with MG. Comparisons will be made with the properties of B lymphocytes and immunoregulatory cells in: 1) autologous blood; and, 2) thymic cell suspensions of control subjects. Specifically, we will determine: 1) if anamolous activity of MG B lymphocytes reflects unique properties of these cells or the immunoregulatory milieu to which they are exposed; 2) the identity of the la-positive cells found by us to be increased in frequency in MG thymus cell suspensions; and, 3) if MG thymus contains an unique B cell activator. Increased knowledge of the mechanism underlying the augmented thymic B cell response in MG will likely enhance our understanding of aberrant local intrathymic immune events and ultimately may help to clarify mechanisms responsible for initiation, potentiation, and/or perpetuation of disease.